TOWARD IMAGING GLYCOTOOLS BY CLICK COUPLING - Click Chemistry in Glycoscience: New Developments and Strategies - page 191

[ 18 F ]F -

CuSO 4
Na ascorbate
H 2 O

MsO O O

18 F

O O

t BuOH, 100 °C

5 5

O

HN

OR

O N

R'O

O

O

R RO

N
N

OR

18 F

O O

N

N

N

57 R' = Tr, H 58 R = Ac, H

N

18 F

O O

SCHEME 7.12 Synthesis of 18 F labeled triazolyl-glucose and triazolyl-thymidine.

that is, CuSO 4 and sodium ascorbate in t BuOH/H 2 O mixture were used. AZT and
5 - O -trityl AZT reacted under the same conditions to give rise to triazoles 57 . Labeled
derivatives of AZT obtained by CuAAC have also been patented [64].

7.3.3.3 Oligonucleotides Oligonucleotide-based probes are promising tools in
molecular imaging, for example, to detect the expression of specific genes in a
noninvasive way. Labeling oligonucleotides is still a challenging problem due to the
complexity of these molecules. Click chemistry can help to solve the problem by
the use of suitable prosthetic groups. Several ways to label nucleotides have been
investigated taking advantage of CuAAC. For example, thymidine has been elaborated
to several derivatives having an alkyne function at position 5 or an azide function at
position 3 (Scheme 7.13) [68]. Thymidine was protected at 3 position and oxidized
at 5 to give aldehyde 59 . The latter was elaborated to azide 60 and to alkyne 62 .Both
compounds have been used to anchor prosthetic groups bearing an iodoaryl function
suitable for 11 C labeling as shown in structures 61 and 63 . Compounds 61 , 62, and 63
have been transformed into the corresponding phosphoramidites which were used for
oligonucleotide synthesis. The protected thymidine derivative 64 was reacted under
classical conditions with benzylazide 65 bearing a di- t -butylsilyl group at the para
position to give 66 . The silicon group of 66 is suitable for

18 F labeling by simple

treatment with [ 18 F]F − [69-72].
As shown in Scheme 7.14, the labeling using this approach has been studied in
detail in a subsequent paper [73]. For example, 5 -azido thymidine 67 was coupled
with the propargyl ether 68 to give 69 in very high yield at high temperature with
the help of microwave irradiation under classical catalysis by copper sulfate and
sodium ascorbate. The labeled fluoride 70 was obtained from 69 in good radiochem-
ical yield (34% not decay corrected). Compound 69 was further elaborated to the
phosphoramidite 71 under classical conditions and engaged in an automated deoxy-
oligonucleotide synthesis to provide 72 .[ 18 F]-fluorination of 72 as above provided